What does the literature say regarding the administration of intravesical aminocaproic acid in management of intractable bladder hemorrhage. At what rate does the bladder irrigation run and for how long?

Comment by InpharmD Researcher

Data evaluating intravesical aminocaproic acid for intractable bladder hemorrhage appears scarce. One case series evaluating intravesical instillation of EACA reported improvements in hematuria, but noted lack of replication in recent studies. Additionally, a randomized controlled trial (RCT) assessing intravesical EACA for post-transurethral resection of the prostate (TURP) bleeding found no significant difference in blood loss between EACA and placebo.

Background

A 2019 Best Practice Report by the Canadian Urological Association conducted a comprehensive narrative synthesis on the diagnosis and management of radiation-induced hemorrhagic cystitis, with a specific emphasis on treatment options, clinical outcomes, and the grading of evidence. The panel states that several intravesical options have been trialed in limited case series, but require replication, etiology-specific assessment, or comparative data before they can be formally included as recommendations. Intravesical instillation of epsilon aminocaproic acid (EACA) was evaluated in a case series from 1992 involving 37 patients with intractable bladder hemorrhage. The study reported improvement in hematuria in 34 of these patients, the majority of whom suffered from cystitis induced by radiation or cyclophosphamide treatment. Despite these promising results, similar studies have not been replicated in recent years to confirm the efficacy of EACA for this condition. Available review articles note that intravesical aminocaproic acid is still used anecdotally in clinical practice, despite sparse evidence of its utility. [1], [2], [3]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Tables 1-2 for your response.

Safety and efficacy of intravesical aminocaproic acid for bleeding after transurethral resection of prostate
Design	Prospective, randomized, double-blind, controlled clinical trial N= 82
Objective	To determine the safety and efficacy of intravesical administration of aminocaproic acid in patients with post-TURP bleeding
Study Groups	Aminocaproic acid group (n= 40) Placebo group (n= 40)
Inclusion Criteria	Male patients aged 45-95 years admitted for presumed benign prostatic hypertrophy and scheduled to undergo TURP
Exclusion Criteria	Symptomatic congestive heart failure, uncontrolled arrhythmia, past history of thromboembolic or hemorrhagic disease, renal disease with serum creatinine >3.0 mg/dl, hepatic disease with elevated liver enzymes, concurrent administration of warfarin, platelet count <150,000/mm3, prothrombin time or partial thromboplastin time >1.5 times control, known sensitivity to aminocaproic acid
Methods	Patients were randomized to receive either aminocaproic acid or placebo irrigation solution post-TURP. Continuous bladder irrigation was administered at 100 ml/hour for up to three days. Blood loss was assessed by hemoglobin determination in irrigation fluid and urine. Serum samples were collected to check for systemic absorption of aminocaproic acid
Duration	Up to three days post-TURP
Outcome Measures	Post-TURP blood loss
Baseline Characteristics	Characteristic	Aminocaproic Acid Group (n= 40)	Placebo Group (n = 40)
	Age, years	65.1 + 8.5	67.0 + 13.7
	Race White Black Hispanic	10 25 5	15 24 1
	Hemoglobin, gm/dl	13.5 + 1.7	13.6 + 1.8
	Hematocrit, %	40.7 + 5.0	41.3 + 5.3
	Platelets, x 103/mm³	254.4 + 75.9	262.0 + 85.9
	Prothrombin time, sec	11.8 + 0.7	11.8 + 0.6
	Partial thromboplastin time, sec	29.9 + 4.4	30.2 + 5.0
Results	Group	Day 1	Day 2	Day 3
	Aminocaproic acid group Mean blood loss, ml Median blood loss, ml Range	23.6 16.9 0.4-81.4	14.0 8.4 2.1-81.3	19.3 8.1 3.5-26.2
	Placebo group Mean blood loss, ml Median blood loss, ml Range	29.9 11.7 0.4-218.9	20.0 13.8 0.3-91.4	28.2 14.4 0.1-83.9
Adverse Events	Adverse effects occurred in 5 aminocaproic acid patients and 5 placebo patients. Transient biochemical abnormalities such as eosinophilia, monocytosis, and elevated LDH and uric acid levels were observed but were not associated with clinical symptoms. Clot retention occurred in one patient from each group.
Study Author Conclusions	There appears to be no clinically significant difference in blood loss or transfusion requirements between intravesical aminocaproic acid and sodium chloride irrigation post-TURP. Intravesical aminocaproic acid might be a useful alternative to systemic antifibrinolytic therapy for delayed, recurrent post-prostatectomy bleeding.
Critique	The study was well-designed as a prospective, randomized, double-blind, controlled trial, which strengthens the validity of the findings. However, the small sample size and the lack of significant differences in outcomes between groups limit the conclusions that can be drawn. Additionally, the study did not specifically evaluate the efficacy of aminocaproic acid in cases of delayed bleeding, which is a potential limitation.

References:

Sharifi R, Lee M, Ray P, Millner SN, Dupont PF. Safety and efficacy of intravesical aminocaproic acid for bleeding after transurethral resection of prostate. Urology. 1986;27(3):214-219. doi:10.1016/0090-4295(86)90277-3

INTRAVESICAL EPSILON AMINOCAPROIC ACID IN MANAGEMENT OF INTRACTABLE BLADDER HEMORRHAGE
Design	Retrospective study N= 37
Objective	To assess the efficacy of intravesical epsilon aminocaproic acid (EACA) given as continuous bladder irrigation in patients with intractable vesical bleeding
Study Groups	All patients (n= 37)
Inclusion Criteria	Patients hospitalized for intractable bladder hemorrhage between 1974 and 1985, excluding those with traumatic and postoperative bleeding
Exclusion Criteria	Patients with traumatic and postoperative bleeding
Methods	Patients received continuous bladder irrigation with EACA. To each liter of 0.9% sodium chloride solution, 200 mg of EACA was added. The irrigation rate was adjusted based on bleeding severity and continued for 24 hours after urine clearance. If bleeding recurred, the protocol was repeated. Treatment was considered a failure if no response was seen within 96 hours or if bleeding recurred a second time.
Duration	1974 to 1985
Outcome Measures	Response to intravesical EACA treatmen, time to response, recurrence of bleeding
Baseline Characteristics		All patients (n= 37)
	Age, mean years	51
	Male	9
	Female	28
	Coagulation profile within normal limits	37
	Blood transfusion required	5
Results		No. of Patients	Responders	Percentage
	Radiation cystitis	14	13	92.6
	Cyclophosphamide-induced cystitis	9	9	100
	Interstitial cystitis	5	5	100
	Carcinoma of bladder	3	1	33.3
	Idiopathic	6	6	100
	TOTALS	37	34	91.9
Adverse Events	No side effects were noted
Study Author Conclusions	Intravesical EACA is a safe and effective method to control intractable bladder hemorrhage, particularly in cases of radiation cystitis and cyclophosphamide-induced cystitis.
Critique	The study demonstrates the effectiveness of intravesical EACA in managing bladder hemorrhage with a high response rate and no reported side effects. However, the retrospective design and lack of serum level measurements are limitations. The study's findings may not be generalizable to all patient populations, particularly those with tumor-induced cystitis where the response was less favorable.

References:

Singh I, Laungani GB. Intravesical epsilon aminocaproic acid in management of intractable bladder hemorrhage. Urology. 1992;40(3):227-229. doi:10.1016/0090-4295(92)90479-g