• 
• 

Three Part Question

In [patients presenting to the emergency department with priapism], does the [use of oral terbutaline] result in [detumescence]

Clinical Scenario

A 46 year old man presents with a painful erection lasting approximately 4 hours. Your attending physician recommends giving oral terbutaline to the patient, but cannot recall the effectiveness of this drug in the treatment of acute priapism.

Search Strategy

Medline 1948 to March Week 5 2011 using OVID interface, Cochrane Library (2011), PubMed clinical queries.
[(exp priapism/ or priapism.mp) AND (exp terbutaline/ or terbutaline.mp or bricanyl.mp)]

Search Outcome

13 papers were found of which only 3 were clinical trials relevant to the three part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Priyadarshi S, 2003, India	68 men between the ages of 24y and 65y with erectile dysfunction with erection lasting more than 2.5 hours after treatment with between 0.1 and 0.5ml of "bimix" (29.25mg papaverine and 0.625mg chlorpromazine per 1ml) solution by intracorporeal injection. Etiology of erectile dysfunction was labeled as psychogenic in 31 patients, neurogenic in 13, and vasculogenic in 34 patients. Patients were randomized by computer to two study arms. The first group received 5mg of terbutaline, with repeat 5mg dosage if detumescence had not occurred at the 15 minute mark, and a third dose if detumescence was not reached by the 30 minute mark. The second group received sodium bicarbonate (initial dosage unknown, and it is unclear if repeat dosing was performed). If detumescence had not occurred by 4 hours, patients in both groups were treated by intracorporeal irrigation with dilute adrenaline solution.	Single center prospective randomized controlled clinical trial.	Detumescence with terbutaline.	14 of 30 patients in the treatment group. Detumescence was achieved in 4/16 psychogenic patients, 4/6 neurogenic, and 6/12 vascular impotence patients.	Small study size, no mention of blinding in methods, no standard dosage of "bimix" implicated in the priapism, unclear which patients had impotence of multiple etiology, unclear what dosage of sodium bicarbonate used and if the dose was repeated in patients not responding to the initial dose, no clear definition of "detumescence" as an endpoint.
			Detumescence with placebo.	5 patients in the placebo group. Detumescence was achieved in 1/15 psychogenic, 1/7 neurogenic, and 3/12 vasculogenic impotence patients.
			Failure of detumescence.	All patients who did not respond to treatment responded to intracorporeal irrigation. No surgical intervention was needed in any patient.
Lowe FC et al 1993, USA	75 men with erectile dysfunction and erections lasting greater than 2.5 hours after intracorporeal injection of 2 to 20 micrograms of prostaglandin E1. Patients were randomized into three treatment arms. Group one received 60mg oral pseudoephrine, group two received 5mg terbutaline sulphate (repeated after 15 minutes if detumescence had not occurred), and the third group received 648mg of sodium bicarbonate. Erections lasting longer than three hours were treated with 2-4ml intracorporeal injection of phenylephrine (0.1mg/ml). Patients were further classified as to the aetiology of erectile dysfunction; 30 attributed to psychogenic, 17 to neurogenic, and 28 to arteriogenic causes. Randomization of patients resulted in similar aetiology, age, and dose of prostaglandin E1 distribution among the groups.	Multicenter prospective randomized controlled trial.	Detumescence with terbutaline.	9 patients responded in the terbutaline group, 3 of which required a total dose of 10mg. Terbutaline worked in 2/11 psychogenic, 4/7 neurogenic, and 3/7 arteriogenic patients.	No mention of blinding, pseudoephrine group had nearly twice as many arteriogenic patients and nearly one third less psychogenic patients, small study size, no clear definition of what was considered "detumescence".
			Detumescence with pseudoephrine.	Pseudoephrine worked in 0/7 psychgenic, 1/5 neurogenic, and 6/13 arteriogenic patients.
			Detumescence with placebo.	Placebo worked in 0/12 psychogenic, 1/5 neurogenic, and 2/8 arteriogenic patients.
				Terbutaline was found to be significantly different than placebo (p<0.05) and equal to pseudoephedrine, but there was no difference between pseudoephrine and placebo.
Govier et al, 1993, USA	22 patients with erectile dysfunction who had an erection lasting greater than 2 hours after an intracorporeal injection of either 0.25ml or 0.5ml of a three drug mixture (22.4mg/ml papaverine, 0.83mg/ml phentolamine, and 8.33microg/ml prostaglandin E1) were randomized into three groups. Group one received a placebo, group two received 2.5mg oral terbutaline, and group three received 5mg oral terbutaline. Patients were sent home and told to return if erection lasted past 4 hours for intracorporeal drainage with or without alpha-agonists. If patients did not return,they were contacted the following day by telephone to obtain information about their detumescence. Detumescence was defined as 75% or less rigidity.	Single center prospective randomized, double-blinded control trial.	Detumescence with 2.5mg terbutaline.	Achieved in 4/7.	Power of study was only 0.15 with a small number of patients. The end point was reported by patients and not monitored by physicians. There was no consistency or reporting of initial dose of erection-stimulating medication, no report on cause of impotence or other historical data on patients. There was no mention of what was used as placebo.
			Detumescence with 5mg terbutaline.	Achieved in 5/8.
			Detumescence with placebo.	Achieved in 4/9.
				There was no significant difference in time to detumescence between the three treatment arms.

Comment(s)

Few studies exist evaluating the use of oral terbutaline in priapism. While both the study by Priyadarshi and the study by Lowe and Jarow seem to show some positive effect, both studies are small and over half of the patients in the treatment groups still required intracorporeal drainage/irrigation. Furthermore, these studies all deal with patients who have had pharmacologically induced priapism through intracorporeal injection. This is not the "typical" patient that would present to an ED; no controlled trials exist on the use of terbutaline in those suffering from priapism from sickle cell disease, oral medications, or other causes. The mechanism of action of terbutaline in erection is poorly understood. Although it acts as a beta-2-agonist and smooth muscle relaxant, the stagnant blood in priapism would impede perfusion of the terbutaline into the corpus cavernosum, suggesting an alternate means of effect, if any.

Clinical Bottom Line

There is no data to recommend routine use of oral terbutaline in cases of priapism presenting to the Emergency Department, and little data to support terbutaline's use in priapism caused by intracorporeal injection of pharmacologic stimulants.

References

1. Priyadarshi S Oral terbutaline in the management of pharmacologically induced prolonged erection. International Journal of Impotence Research October 2004; 424-6
2. Lowe FC, Jarow JP. Placebo-controlled study of oral terbutaline and pseudoephedrine in management of prostaglandin E1-induced prolonged erections. Urology July 1993; 51-3
3. Govier FE, Jonsson E, Kramer-Levien D. Oral terbutaline for the treatment of priapism. The Journal of Urology April 1994; 878-9.