Priapism

Priapism is defined as an abnormal persistent erection of the penis. It is usually painful and it is unrelated to sexual stimulation and unrelieved by ejaculation. Priapism is frequently idiopathic in etiology but it is a known complication of a number of important medical conditions and pharmacologic agents (see Etiology).[6]

Priapism must be identified as either low-flow (ischemic) or high-flow (nonischemic), because the causes and treatments for these 2 types are different. Low-flow priapism, which is by far the most common type, results from failure of the detumescence mechanism, whereas high-flow priapism results from uncontrolled arterial inflow, often through fistulas caused by genitourinary trauma.

Treatment of low-flow priapism should progress in a stepwise fashion, starting with therapeutic aspiration, with or without irrigation, or intracavernous injection of a sympathomimetic agent.[7] Treatment of high-flow priapism focuses on identification and obliteration of fistulas.

Priapism is a true urologic emergency that may lead to permanent erectile dysfunction and penile necrosis if left untreated. Early intervention allows the best chance for functional recovery[6] ; as with many medical emergencies, the saying "time is tissue" holds true for priapism.

The penis has 3 corporeal bodies: 2 corpora cavernosa and 1 corpus spongiosum. Erection is the result of smooth-muscle relaxation and increased arterial flow into the corpora cavernosa, causing engorgement and rigidity (see image below). In priapism, the corpus spongiosum and glans penis are typically not engorged.

Priapism. Corporeal relaxation causes external pressure on the emissary veins exiting the tunica albuginea, trapping blood in the penis and causing erection.

Engorgement of the corpora cavernosa compresses the venous outflow tracts (ie, subtunical venules), trapping blood within the corpora cavernosa. The major neurotransmitter that controls erection is nitric oxide, which is secreted by the endothelium that lines the corpora cavernosa (see image below). These events occur in both normal and pathologic erections.

Priapism. Sexual stimulation causes the release of nitric oxide (NO) via stimulation of nonadrenergic noncholinergic neurons. NO-activated intracellular guanylate cyclase, converting guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), causes relaxation of cavernosal arteries and increased penile blood flow, resulting in erection.

Pathophysiologically, priapism can be of either a low-flow (ischemic) or a high-flow (nonischemic) type. Low-flow priapism, which is by far the most common type, results from failure of venous outflow, whereas high-flow priapism results from uncontrolled arterial inflow. Clinically, differentiation of low-flow from high-flow priapism is critical, because treatment for each is different.

Low-flow priapism may be due to any of the following:

• An excessive release of neurotransmitters

• Blockage of draining venules (eg, mechanical interference in sickle cell crisis, leukemia, or excessive use of intravenous parenteral lipids)

• Paralysis of the intrinsic detumescence mechanism

• Prolonged relaxation of the intracavernous smooth muscles (most often caused by the use of exogenous smooth-muscle relaxants such as injectable intracavernosal prostaglandin E1)

Prolonged low-flow priapism leads to a painful ischemic state, which can cause fibrosis of the corporeal smooth muscle and cavernosal artery thrombosis. The degree of ischemia is a function of the number of emissary veins involved and the duration of occlusion. Light-microscopy studies conducted early on demonstrated that corporeal tissue becomes thickened, edematous, and fibrotic after days of priapism.

Further studies with electron microscopy have demonstrated trabecular interstitial edema after 12 hours of priapism and destruction of sinusoidal endothelium, exposure of the basement membrane, and thrombocyte adherence after 24 hours of priapism. At 48 hours, thrombi were evident in the sinusoidal spaces and smooth-muscle cell histopathologic findings varied from necrosis to fibroblast-like cell transformation. Priapism for longer than 24 hours is associated with the likelihood of permanent impotence.

High-flow priapism is the result of uncontrolled arterial inflow from a fistula between the cavernosal artery and the corpus cavernosum. This is generally secondary to blunt or penetrating injury to the penis or perineum causing rupture of a cavernous artery. It is usually not painful.

Priapism can be idiopathic or can be secondary to a variety of diseases, conditions, or medications. In the United States, the most common cause of priapism in the adult population involves agents used to treat erectile dysfunction. Internationally, most cases are idiopathic.

The most common cause of priapism in the pediatric population is sickle cell disease (SCD), which is responsible for 65% of cases. Leukemia, trauma, and idiopathic causes are the causes in 10% of patients. Pharmacologically induced priapism is the etiology in 5% of children.[8] Among the secondary causes of low-flow priapism are the following thromboembolic/hypercoagulable states:

• Sickle cell anemia - One study found that, in unscreened children with SCD, priapism was the first presentation in 0.5% of cases ^[4]
• Thalassemia
• Fabry disease
• Dialysis
• Vasculitis
• Fat embolism (from multiple long-bone fractures or intravenous infusion of lipids as part of total parenteral nutrition)

Neurologic diseases that can result in low-flow priapism include the following:

• Spinal cord stenosis (ie, trauma to the medulla)
• Autonomic neuropathy and cauda equina compression

Neoplastic disease (metastatic to the penis or obstructive to venous outflow) that can result in low-flow priapism include the following[9] :

• Prostate cancer
• Bladder cancer (highest risk)
• Hematologic cancer (leukemia)
• Renal carcinoma
• Melanoma

Pharmacologic causes of low-flow priapism include the following:

• Intracavernosal agents - Papaverine, phentolamine, prostaglandin E1
• Intraurethral pellets (ie, medicated urethral system for erection with intracavernosal prostaglandin E1)
• Antihypertensives - Ganglion-blocking agents (eg, guanethidine), arterial vasodilators (eg, hydralazine), alpha-antagonists (eg, prazosin), calcium channel blockers
• Psychotropics - Phenothiazine, butyrophenones (eg, haloperidol), perphenazine, trazodone, selective serotonin reuptake inhibitors (eg, fluoxetine, sertraline, citalopram) ^[5]
• Anticoagulants - Heparin, warfarin (during rebound hypercoagulable states)
• Recreational drugs - Cocaine ^[10]
• Hormones - Gonadotropin-releasing hormone (GnRH), tamoxifen, testosterone, androstenedione for athletic performance enhancement
• Herbal medicine - Ginkgo biloba with concurrent use of antipsychotic agents ^[11]
• Miscellaneous agents - Metoclopramide, omeprazole, penile injection of cocaine, epidural infusion of morphine and bupivacaine ^[12]

Only rare case reports have associated phosphodiesterase-5 enzyme inhibitors such as sildenafil with priapism. In fact, several reports suggest sildenafil as a means to treat priapism and as a possible means of preventing full-blown episodes in patients with sickle cell disease.[13]

High-flow priapism may result from the following forms of genitourinary trauma:

• Straddle injury
• Intracavernous injections resulting in direct cavernosal artery injury

Rare causes of priapism include the following:

• Amyloidosis (massive amyloid infiltration)
• Gout (one case report)
• Carbon monoxide poisoning
• Malaria
• Black widow spider bites ^[14]
• Asplenia
• Fabry disease (rare association, occasionally noted to be priapism of the high-flow type)
• Vigorous sexual activity
• Mycoplasma pneumoniae infection (mechanism is thought to be a hypercoagulable state induced by the infection)

A review of United States emergency department visits with a primary diagnosis of priapism from 2006 to 2009 determined that the annual incidence rate was 5.34 per 100,000 males. The rate of visits was 31.4% higher in summer months than in winter months.[15]

The frequency of priapism varies in different populations. The combination of intracavernosal agents and other drugs is the cause of approximately 21-80% of all adult priapism in the United States. Agents used to treat erectile dysfunction are common causes of adult priapism in the Western world. The overall rate of priapism in persons using these agents ranges from 0.05-6%. This group tends to be better educated about the risk of priapism; therefore, they seek treatment earlier.

In other population groups, sickle cell disease (SCD) and sickle cell trait predominate as the cause of adult priapism. The rate of priapism in adults with SCD is as high as 89%. In one study, 38-42% of adult males with SCD reported at least one episode of priapism. Approximately two thirds of all pediatric patients who have priapism also have SCD. The rate of priapism among children with SCD is as high as 27%.

Internationally, the overall incidence of priapism is 1.5 cases per 100,000 person-years. In men older than 40 years, the incidence increases to 2.9 cases per 100,000 person-years.[16, 17]

Racial, sexual, and age-related differences in incidence

No racial predilection toward priapism exists. SCD, which predisposes to the development of priapism, occurs mostly in the African-American population.

Priapism is almost exclusively a disease of males. Priapism of the clitoris has been reported but is extremely rare.[18]

Priapism has been described at nearly all ages, from infancy through old age. A bimodal distribution has been noted, with peaks at 5-10 years and 20-50 years.[16] Cases in younger groups are more often associated with SCD, while those in older groups tend to be secondary to pharmacologic agents.

Prognosis depends on the duration of symptoms, the patient's age, and the underlying pathology. The duration of symptoms is the single most important factor affecting outcome. A Scandinavian study reported that 92% of patients with priapism for less than 24 hours remained potent, while only 22% of patients with priapism that lasted longer than 7 days remained potent.[3]

All patients with priapism should be warned about the long-term risk of erectile dysfunction. The warning should also be clearly written on the discharge instruction sheet and documented in the chart. In general, vaso-occlusive priapism poses a higher risk of impotence than high-flow arterial priapism. Sickle cell disease appears to particularly increase risk: a study by Anele and Burnett found that patients with sickle cell disease who experience even minor episodes of recurrent ischemic priapism are five times more likely to develop erectile dysfunction compared with non–sickle cell patients.[19]

Patients who have experienced an episode of priapism are at risk for recurrence. A review of 3,372 men who presented to emergency departments with priapism found that within 1 year, 24% of patients were readmitted for recurrent priapism. Of those, 68% were readmitted within 60 days.[20]

Infection can complicate priapism. In cases resulting from trauma, the source of the infection may be the trauma itself, or it may be iatrogenic. Corporeal fibrosis due to persistent priapism can result in deep-tissue infections of the penis.

Deaths have been reported in patients with sickle cell disease presenting with priapism, but the cause of death usually is not related to the priapism per se but to complications from the underlying disease process.

Education is the best way to avoid undesirable outcomes. Any high-risk patient, especially a man using oral or intracavernosal agents for the treatment of erectile dysfunction, must understand that a persistent erection is a possibility, and that prompt medical attention is critical if it should occur.

Patients presenting with priapism deserve special counseling, beginning with the first episode of priapism. Patients must understand that a poor outcome is possible despite appropriate and timely management.

For patient education resources, see the Priapism Directory.

Patients with priapism report a persistent erection. Accompanying symptoms depend on the type of priapism and the duration of engorgement. Low-flow, ischemic-type priapism is generally painful, although the pain may disappear with prolonged priapism.

High-flow, nonischemic priapism is generally not painful. This type of priapism is associated with blunt or penetrating injury to the perineum. It may manifest in an episodic manner.

Points to address in the history are as follows:

• Duration of erection (longer than 4 hours is consistent with priapism)
• Duration of pain
• Similar prior episodes (ie, stuttering priapism)
• Genitourinary (GU) trauma
• Medical history (eg, sickle cell disease [SCD]): Onset occurs during sleep, when relative oxygenation decreases
• Medication and/or recreational drug use, especially the antidepressant trazodone, intracavernosal injections of prostaglandin E1 used to treat impotence, and illicit cocaine injection into the penis
• History of malignancy (eg, prostate cancer, bladder cancer)
• Penile prosthesis: The permanent erection that occurs with some penile prostheses may mimic priapism
• Recent urologic surgery

Historical features of low-flow priapism include the following:

• Painful
• Patient is inactive sexually and without desire
• No history of trauma
• Patient usually presents to emergency department (ED) within hours
• Associated with substance abuse or vasoactive penile injections
• Rare causes include leukemia, fat embolism, acute spinal cord injury, or (extremely rare) cancer metastases to the corporeal bodies

Historical features of high-flow priapism include the following:

• Not painful
• The patient may be sexually active
• Straddle injury usually the initiating event
• Chronic recurrent presentation
• Generally not caused by medication
• Delay may exist between the initiating injury and the onset of priapism (eg, because of initial vessel spasm or to the formation of a clot that is gradually reabsorbed over a period of days)

Obvious erection is the key physical finding in any case of priapism. Penile priapism generally involves only the paired corpora cavernosa, with the glans and corpora spongiosum remaining flaccid or softly distended without rigidity. Careful physical examination may reveal specific causal factors. Remember that no single pathology excludes all others; therefore, a thorough history and physical examination should address the patient as a whole.

Points to address in the physical examination are as follows:

• Penile color, rigidity, and sensation (soft glans vs firm glans)
• Penile discharge, lesions, or both
• Evidence of local trauma or injection sites
• Presence of prosthetic devices (hardware malfunction may cause pseudopriapism)
• Regional lymphadenopathy (ie, metastatic disease)
• Rectal tone: High spinal cord lesions or stenosis may cause priapism

Aspects of the physical examination consistent with low-flow priapism are as follows:

• Rigid erection
• Ischemic corpora as indicated by dark blood upon corporeal aspiration
• No evidence of trauma

Aspects of the physical examination consistent with high-flow priapism are as follows:

• Adequate arterial flow
• Well-oxygenated corpora
• Evidence of trauma

In young children, the presence of the Piesis sign (prompt detumescence upon perineal compression with the examiner’s thumb) indicates high-flow priapism.

A complete blood cell count (CBC) should be performed to determine whether the patient has anemia, leukocytosis, or thrombocytosis. Rarely, the CBC will identify undiagnosed leukemia as the cause of priapism.

Patients with sickle cell disease should have a CBC and a reticulocyte count. If sickle cell status is unknown, a hemoglobin S determination may be useful. Patients with sickle cell disease may also need a blood type and screen performed in case transfusion or plasma exchange is necessary.

Measurement of plasma thromboplastin or activated partial thromboplastin time to determine coagulation status may be useful, as priapism may require surgical intervention if medical treatment fails.

Penile blood gas (PBG) test results allow differentiation between high- and low-flow priapism. Low-flow PBG findings may include a pH of less than 7.0, a PCO2 of greater than 60 mm Hg, and a PO2 of less than 30 mm Hg. Variation depends on the duration of the episode. In high-flow priapism, PBG findings should reflect normal arterial values.

Urine toxicology and psychoactive medication screening should be considered, in suspected patients, as some of these medications are known to cause priapism in standard doses or overdoses.

Color-flow penile Doppler imaging is currently the study of choice to differentiate high-flow from low-flow priapism. In patients with high-flow priapism, ultrasonography can help identify and locate fistulas. In a study of 52 patients, von Stempel et al found that on Dopper ultrasonography, a peak systolic velocity of less than 50 cm/sec and a mean velocity of less than 6.5 cm/sec were predictive of ischemic priapism.[21]

In patients with high-flow priapism, selective penile angiography may be required in order to identify the site of the fistula, or to confirm the location of a fistula identified by ultrasound. The fistula can then be closed by embolization.

Perform chest radiography or computed tomography (CT) scanning if the history is consistent with a malignant or metastatic condition. Perform an electrocardiogram if the patient is older than 55 years, has a history of cardiac disease, or is a possible surgical candidate.

Appropriate treatment of priapism varies, depending on whether the patient has low-flow or high-flow priapism. Most priapism cases are the low-flow ischemic type.

Treatment of low-flow priapism should progress in a stepwise fashion, starting with therapeutic aspiration, with or without irrigation, followed by intracavernous injection of a sympathomimetic agent. Repeated injection of a sympathomimentic agent should be performed before considering surgical intervention.[7] Although all cases of priapism require prompt consultation with a genitourinary medicine specialist, emergency department (ED) personnel who have appropriate training and protocols may begin treatment with saline irrigation and injection. Treatment of high-flow priapism focuses on identification and obliteration of fistulas.

In patients with priapism secondary to other disorders, attempt to treat the underlying condition whenever possible. Treatment for priapism secondary to sickle cell disease includes hydration, alkalization, analgesia, and oxygenation to prevent further sickling. Hypertransfusion and/or exchange transfusions may be required to increase the hemoglobin concentration to higher than 10% and decrease hemoglobin S to less than 30%. In a study of 239 exchange transfusions performed in adult patients with sickle cell disease and major priapism refractory to other medical therapies, Ballas and Lyon reported that none of the patients developed any neurological complications (eg, headache, seizures, neurological deficits, obtundation).[22]

The potential medical and legal pitfalls in the treatment of priapism deserve special attention. Meticulous documentation is essential and helps protect the physician from future litigation by a patient who may be upset by a poor outcome despite appropriate management and careful counseling at the time of treatment.

Prompt treatment and referral to a urologist is strongly encouraged. At least 50% of patients with priapism have persistent impotence, either because of the priapism event or its treatment, and legal liability exposure is higher than that seen in many other urologic diseases.

Any patient who has an erection for longer than 4 hours, especially if he has a predisposing illness (eg, sickle cell disease) probably should receive therapy for priapism. Most cases, if seen early enough in their course, respond to conservative measures.

Examples of immediate treatment that can be suggested prior to arrival at the hospital may include the use of ice packs to the perineum and penis or asking the patient to walk up stairs. The latter strategy is thought to work via an arterial steal phenomenon. External perineal compression may also be a useful temporizing measure in the ED or prehospital setting. If these measures fail to produce rapid detumescence, patients should not delay transfer to the hospital.

Treatment should progress in a stepwise fashion, accompanied by supportive care and the identification and treatment of reversible causes. Intracavernosal phenylephrine is the drug of choice and first-line treatment of low-flow priapism because the drug has almost pure alpha-agonist effects and minimal beta activity. In short-term priapism (< 6 h), especially drug-induced cases, intracavernosal injection of phenylephrine alone may result in detumescence.

Some studies suggest that oral terbutaline orally, at a dose of 5-10 mg, followed by another 5-10 mg 15 minutes later, if required, produces resolution in about one third of patients. Oral pseudoephedrine, 60-120 mg orally has also been suggested as a potential therapy due to its alpha-agonist effect. The exact efficacy of this medication orally is unknown. Oral agents may be a reasonable treatment option to use while preparing for aspiration/injection. If no resolution occurs within 30 minutes, injection therapy is required.

Long-term, continuous use of phosphodiesterase type 5 (PDE5) inhibitors (eg, sildenafil), although off-label, has shown benefit in controlling recurrent ischemic priapism.[13] A retrospective study of regimented PDE5 inhibitor dosing in patients with recurrent ischemic priapism found that of 24 evaluable patients, 22 (92%) reported improvement in priapism outcomes, with nine patients reporting resolution. Priapism-related emergency department visits per month decreased 4.4-fold; duration and frequency of priapism also decreased significantly.[23]

Similarly, evidence supporting noninvasive treatment of ischemic priapism is sparse, but attempting it poses minimal risk as long as it does not delay the use of more definitive treatment. Conservative treatments described in the literature include application of an ice pack, cold showers, masturbation, and lower-limb exercise (eg, stair climbing).[24]

Aspiration/injection of the corpus cavernosum

First perform a penile nerve block. Inject around the entire base of the penile shaft with 1% lidocaine without epinephrine or bupivacaine without epinephrine. Providing anesthesia will increase patient comfort and improve patient cooperation with the sometimes-painful penile aspiration procedure.

After anesthesia is ensured, use a 19-gauge needle attached to a large syringe to puncture the corpus cavernosum. The needle should be inserted through the shaft of the penis laterally to avoid the corpus spongiosum and urethra ventrally and the neurovascular bundle dorsally.

Aspirate 20-30 mL of blood from either the 2-o'clock or 10-o'clock position while milking the shaft. Because multiple communications exist from one corpus to the other, aspiration usually is required on one side only. If initial aspiration of the corpus cavernosum reveals bright red blood rather than dark venous blood, consider an arterial cause for priapism and treat as for high-flow cases.

Aspiration alone has a success rate of around 30%. Aspiration may be difficult because of the sludging of blood within the corpus cavernosum. Saline irrigation and repeated aspirations may improve flow dynamics. If this procedure is not successful, phenylephrine, epinephrine, or methylene blue may be instilled into the corpus cavernosa.

For the injection, use a mixture of 1 ampule of phenylephrine (1 mL:1000 mcg) and dilute it with an additional 9 mL of normal saline. Using a 29-gauge needle, inject 0.3-0.5 mL into the corpora cavernosa, waiting 10-15 minutes between injections. Monitor vital signs and apply compression to the area of injection to help prevent hematoma formation.

If phenylephrine is not available, epinephrine can be used.[25] However, epinephrine has more adverse effects and is considered second-line treatment. Another second-line treatment is instillation of methylene blue.

Alternatively, the corpora cavernosa can be irrigated with a diluted solution of phenylephrine. A diluted solution can be infused 10-20 mL at a time.

If aspiration or injection is successful in producing detumescence, place an elastic bandage around the shaft of the penis to ensure continued emptying of the corpora and to compress the puncture site.

For full description of these procedures, see Penile Injection and Aspiration.

Acutely, observation alone may be sufficient for high-flow priapism, because many cases resolve spontaneously, and even with prolonged priapism these patients are unlikely to experience significant pathological damage or impaired erectile function. Compression therapy may be successful in certain cases, especially children; continuous compression may be maintained with a strap-on dressing.[16]

Selective angiography with subsequent embolization of the offending vessel has been shown to be effective with few long-term complications in some studies. Selective arterial embolization can be done using autologous blood clot, gelatin sponge, microcoils, or chemicals.[26, 27, 7] Patients who do not respond to more conservative measures may benefit from this approach.

Surgical ligation of the fistula may be required. However, potential complications of this procedure include long-term impotence.

Distal shunt in the form of a transglanular-to-corpus cavernosal scalpel or needle-core biopsy (Ebbehoj or Winter technique) is the first reasonable approach for refractory cases (see image below). A unilateral shunt is often effective. Bilateral shunts are used only if necessary (usually apparent after 10 min).

Priapism. Winter shunt placed by biopsy needle, usually under local anesthetic.

The El-Ghorab procedure is a more aggressive open surgical cavernosal shunt and is indicated if the Winter shunt fails.

For patients with prolonged low-flow priapism, some authors recommend considering caverno-dorsal vein shunting (Barry shunt). In this procedure, the surgeon transects the superficial or deep dorsal vein of the penis and anastomoses it to the corpora cavernosa. An advantage of the procedure is that if priapism recurs priapism during the initial post-surgical period, the patient can “milk” the tumescence into the shunt.[28]

Osomonov et al reported successful caverno-dorsal vein shunting in a patient with 76-hour stuttering priapism, without subsequent erectile dysfunction.[29] Micoogullari et al used caverno-dorsal vein shunting in 10 patients with low-flow priapism that failed to respond to drainage of the corpus cavernosum. Detumescence occurred in all patients, and 8 of the 10 maintained erectile function. Micoogullari et al consider caverno-dorsal vein shunt a treatment of choice for refractory low-flow priapism.[29]

Proximal shunt surgery (eg, Quackel shunts) are cavernosal-spongiosum shunts (unilateral or bilateral) and are performed via a perineal approach (see image below). Such shunts are rarely effective if a more distal shunt (eg, El-Ghorab procedure) has already failed, because thrombosis of the corpora is usually already present.[30]

Priapism. Proximal cavernosal-spongiosum shunt (Quackel shunt) surgically connects the proximal corpora cavernosa to the corpora spongiosum.

A Grayhack shunt is a cavernosal-saphenous vein shunt (rarely necessary or indicated; see image below).

Priapism. Proximal cavernosal-saphenous shunt (Grayhack shunt) surgically connects the proximal corpora cavernosum to the saphenous vein.

Reed-Maldonado propose an algorithm for the treatment of ischemic priapism that uses duration of priapism as decision points. For patients with priapism for less than 24 hours in whom aspiration/injection fails, and in those who present more than 24 hours after onset, these authors recommend the use of anticoagulation with shunting. Anticoagulation consists of aspirin, 325 mg orally, and heparin, 5000 units subcutaneously, given preoperatively. Postoperatively, anticoagulation with aspirin (81 mg/day orally) and clopidogrel (75 mg/day orally) is continued for 5 days.[31]

Prolonged low-flow priapism results in a variable degree of cavernosal fibrosis and a subsequent loss of penile length. The delayed insertion of a penile prosthesis can be difficult, with high complication rates. Immediate insertion of a penile prosthesis in patients with prolonged low-flow priapism is simple and maintains penile length. This may be offered to patients at initial presentation, as the complication rate is low and the subsequent outcome excellent.[32, 33, 34, 35]

Fuchs et al describe successful use of corporal decompression through a penoscrotal approach for treatment of ischemic priapism that has failed to respond to distal shunt procedures. In this technique, the initial incision and dissection are identical to those used for implantation of a penoscrotal inflatable penile prosthesis; an approximately 2-cm incision is then made in the corpora, corporal decompression is performed using a pediatric Yankauer suction tip, and the sludged blood is expressed with firm manual pressure.[36]

In a case series, this approach was effective in 6 of 6 patients with prolonged ischemic priapism that was refractory to multiple prior treatments, including at least 1 distal shunt. All patients required no additional intervention and all noted immediate relief of pain postoperatively. In contrast, in an earlier series of similar cases treated with placement of a malleable penile prosthesis, 3 of the 8 patients required a total of 8 revision surgeries during a median follow-up of 41.5 months.[36]

Key steps in the management of sickle cell disease–associated priapism include oxygenation, analgesics (eg, intravenous morphine), hydration, alkalization, and exchange transfusions to increase the hematocrit value to greater than 30% and to decrease the hemoglobin S (HbS) value to less than 30%. Although conservative management has commonly been advocated in the literature, several studies have questioned its efficacy, and most experts advocate emergent surgical decompression when conservative management fails.

Ekong and colleagues reported successful use of automated red cell exchange transfusion (ARCET) in five patients with sickle cell disease who were experiencing severely affected by stuttering priapism. Immediately after undergoing ARCET, with a target post-transfusion HbS level below 10%, all five became completely free of stuttering priapism. All five experienced recurrences as their HbS percentage increased towards the end of the ARCET cycle, but with subsequent cycles, most of the patients remained essentially free of stuttering priapism.[37]

Priapism in females is extremely rare but has been described. No single therapy has been shown to be effective. Consider terbutaline in the first instance and consultation with a urologist.

Neonatal priapism may result from birth trauma or other conditions at birth.

Stuttering or recurrent priapism may occur in patients with sickle cell trait or disease. Usually self-limiting in nature, over time such episodes may lead to erectile dysfunction.

Early consultation with a urologist is recommended, especially when less-invasive measures in the ED fail to resolve priapism or a high-flow condition is suspected. If a urologist is not available at the presenting institution, the patient should be transferred to an appropriate tertiary care center where a urologist is available. Refractory priapism may require urologic consultation for placement of a corpus cavernosum–corpus spongiosum shunt.

Consultation with a cardiologist may be appropriate for patients with cardiac disease or hypertension. Consultation with a hematologist is indicated for patients whose priapism is a complication of SCD.

Ensure adequate follow-up care with a urologist if therapy in the ED is successful. Patients with identified underlying disorders should follow up with the appropriate specialist.

Some patients may have recurrent priapism. These patients may be prescribed a home supply of terbutaline. Instruct these patients on how to self-administer this medication either as a 5-mg tablet or a 0.25-0.5 mg subcutaneous injection prior to presentation.

Patients with sickle cell disease may also benefit from intramuscular leuprolide (Lupron) injections prescribed by a urologist. Leuprolide is a gonadotropin-releasing hormone (GnRH) agonist and thus should be avoided in patients who have not fully matured sexually.[7]

A small study (in 8 patients) describes suppression of testosterone with ketoconazole and prednisone for treatment of recurrent priapism.[38] In a more recent study involving 17 patients, starting ketoconazole at 200 mg 3 times daily and prednisone at 5 mg daily for 2 weeks, then tapering to ketoconazole 200 mg nightly for 6 months, proved reasonably effective, safe, and inexpensive.[39] This therapy should be initiated by a urologist because testosterone measurements may be necessary to monitor therapy.

Finasteride proved effective for preventing recurrent priapism in a study of 5 adolescents and children with sickle cell disease; most of these patients responded to a dosage of 1 mg a day.[40] Several other treatments have been reported with variable success rates, including phosphodiesterase-5 enzyme (PDE-5) inhibitors, antiandrogens, and other medications.[13, 40, 41, 42, 43]

American Urological Association guideline

The American Urological Association (AUA) published a guideline on the management of priapism in 2003.[7] The guideline was reviewed and its validity confirmed in 2010.[7]

The AUA guideline advises that to initiate appropriate management, the physician must determine whether the priapism is ischemic or nonischemic. For example, in ischemic priapism, full rigidity of the corpora cavernosa, penile pain, and abnormal cavernous blood gases are usually seen, while blood abnormalities, hematologic malignancy, or recent intracavernous vasoactive drug injections are sometimes seen. In nonischemic priapism those are seldom present, but chronic, well-tolerated tumescence without full rigidity is usually present, and patients sometimes have a history of perineal trauma.

The guideline also includes recommendations on treatment of recurrent (stuttering) priapism.

Treatment recommendations for ischemic priapism include the following:

• In patients with an underlying disorder (eg, sickle cell disease, hematologic malignancy), ischemic priapism requires intracavernous treatment, which should be administered concurrently with systemic treatment of the underlying disorder
• Management of ischemic priapism should progress in a step-wise fashion to achieve resolution as promptly as possible; initial intervention may include therapeutic aspiration (with or without irrigation) or intracavernous injection of sympathomimetics
• If ischemic priapism persists after aspiration/irrigation, intracavernous injection of a sympathomimetic drug should be performed; phenylephrine is recommended, as it poses less risk of cardiovascular side effects than other sympathomimetics
• For intracavernous injections in adult patients, phenylephrine should be diluted with normal saline to a concentration of 100 to 500 mcg/mL and given in 1-mL doses; in children and patients with severe cardiovascular disease, lower concentrations in smaller volumes should be used; injections should be given every 3 to 5 minutes for approximately 1 hour before deciding that the treatment has failed
• During and after intracavernous injection of sympathomimetic drugs, the physician should observe patients for subjective symptoms and objective findings consistent with known undesirable effects of these agents: acute hypertension, headache, reflex bradycardia, tachycardia, palpitations, and cardiac arrhythmia; in patients with high cardiovascular risk, blood pressure and electrocardiogram monitoring are recommended
• Surgical shunts for the treatment of ischemic priapism should be considered only after a trial of intracavernous sympathomimetics has failed
• A cavernoglanular (corporoglanular) shunt should be the first choice of the shunting procedures, because it is the easiest to perform and has the fewest complications; it can be performed with a large biopsy needle (Winter) or a scalpel (Ebbehøj) inserted percutaneously through the glans, or by excising a piece of the tunica albuginea at the tip of the corpus cavernosum (Al-Ghorab); proximal shunting using the Quackels or Grayhack procedures may be warranted if more distal shunting procedures have failed to relieve the priapism

• Oral systemic therapy is not indicated for the treatment of ischemic priapism

Treatment recommendations for nonischemic priapism include the following:

• With nonischemic priapism, corporal aspiration has only a diagnostic role; aspiration, with or without injection of sympathomimetic agents, is not recommended as treatment

• The initial management of nonischemic priapism should be observation

• Immediate invasive interventions (embolization or surgery) can be performed at the request of the patient, but should be preceded by a thorough discussion of chances for spontaneous resolution, risks of treatment-related erectile dysfunction, and that no significant consequences can be expected if intervention is delayed

•  In patients with nonischemic priapism who request treatment, selective arterial embolization is recommended; for interventional radiologic management, autologous clot and absorbable gels, which are non-permanent, are preferable to coils and chemicals, which are permanent

• Surgery is the option of last resort for treatment of nonischemic priapism and should be performed with intraoperative color duplex ultrasonography

Treatment recommendations for stuttering priapism include the following:

• The goal of the management of a patient with stuttering priapism is prevention of future episodes while management of each episode should follow the specific treatment recommendations for ischemic priapism

• A trial of gonadotropin-releasing hormone (GnRH) agonists or antiandrogens may be used in the management of patients with stuttering priapism; however, hormonal agents should not be used in patients who have not achieved full sexual maturation and adult stature

• Intracavernosal self-injection of phenylephrine should be considered in patients who reject systemic treatment of stuttering priapism or in whom it fails

European Association of Urology guidelines

The European Association of Urology released guidelines on the diagnosis and treatment of priapism in 2014.[44] Treatment recommendations include the following:

• Interventions for ischemic priapism, which is an emergency condition, should begin within 4-6 hours and include decompression of the corpora cavernosa by aspiration and intracavernous injection of sympathomimetic drugs
• When conservative management for ischemic priapism fails, surgical treatment is recommended
• For patients with long-lasting priapism, immediate implantation of a prosthesis should be considered
• For arterial priapism, which is not an emergency, selective embolization has high success rates
• The main therapeutic goal for stuttering priapism is prevention of future episodes, which may be achieved pharmacologically (although information on the efficacy of such treatment is limited)

The goals of pharmacotherapy are to reduce morbidity and to restore sexual function. Drugs used include adrenergic agonists and antidotes.

Class Summary

These agents have been used successfully in the treatment of priapism, possibly due to their sympathomimetic vasopressor activity.

Terbutaline has been shown to be effective for the treatment and prevention of priapism, although its mechanism of action in these cases is not yet fully elucidated.

Phenylephrine

Phenylephrine is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body. This agent increases peripheral venous return. The drug is best administered in a dilute solution; add 10 mg (usually 1 mL) of phenylephrine to 499 mL of normal saline, yielding a solution with 20 mcg/mL.

Pseudoephedrine (Sudafed, ElixSure, Unifed, Psudatabs)

An oral dose of 60-120 mg may be given in cases of priapism of short duration (2-4 h). Pseudoephedrine promotes vasoconstriction by directly stimulating alpha-adrenergic receptors.

Terbutaline

Terbutaline is a selective beta2-adrenergic agonist used successfully in the treatment of priapism.

Class Summary

These agents have a second-messenger inhibitory effect, affecting muscle relaxation.

Methylene blue

Methylene blue inhibits smooth muscle relaxation.