Ischemic Priapism (Veno-Occlusive, Low-Flow)

Ischemic priapism is a persistent erection marked by rigidity of the corpora cavernosa and little or no cavernous arterial inflow. In ischemic priapism there are time-dependent changes in the corporal metabolic environment with progressive hypoxia, hypercarbia, and acidosis. The patient typically complains of penile pain after 6 to 8 hours, and the examination reveals a rigid erection. The condition is analogous to a muscle compartment syndrome, with initial occlusion of venous outflow and subsequent cessation of arterial inflows. Well-documented histologic changes occur within the corporal smooth muscle as a consequence of prolonged ischemia. Interventions beyond 48 to 72 hours of onset may help relieve erection and pain but have little benefit in preserving potency. Histologically by 12 hours corporal specimens show interstial edema, progressing to destruction of sinusoidal endothelium, exposure of the basement membrane, and thrombocyte adherence at 24 hours. After 48 hours thrombus can be found in the sinusoidal spaces and smooth muscle necrosis with fibroblast-like cell transformation is evident (Spycher, 1986). Ischemic priapism is an emergency. When left untreated, resolution may take days and erectile dysfunction (ED) invariably results (Fig. 25–1A and B).

Figure 25–1 A, Transverse gray-scale ultrasound image of pendulous penis in a 30-year-old sickle cell disease patient, with history of multiple episodes of priapism, shows hyperechoic corporal fibrosis replacing normal tissues (arrows). B, Color duplex Doppler in same patient following intracavernous injection of alprostadil. The right and left (RCA, LCA) cavernous arteries show preservation of blood flow only at the base of the penis.

Stuttering Priapism (Intermittent)

Stuttering priapism characterizes a pattern of recurrence. The term has historically described recurrent unwanted and painful erections in men with sickle cell disease (SCD) (Serjeant, 1985). Patients typically awaken with an erection that persists for several hours. Unfortunately, males with SCD may experience stuttering priapism from childhood; in these patients the pattern of stuttering may increase in frequency and duration, leading up to a full episode of unrelenting ischemic priapism. Unfortunately, any patient who has experienced an episode of ischemic priapism is also at risk for stuttering priapism.

Nonischemic Priapism (Arterial, High-Flow)

Nonischemic priapism is a persistent erection caused by unregulated cavernous arterial inflow. Typically, the corpora are tumescent but not rigid and the penis is not painful. A history of blunt trauma to the penis or an iatrogenic needle injury is common. Whatever the mechanism of injury, the result is a disruption of the cavernous arterial anatomy creating an arteriolar-sinusoidal fistula. The cavernous environment does not become ischemic and cavernous blood gases do not show hypoxia, hypercarbia, or acidosis. This type of priapism, once properly diagnosed, does not require emergent intervention. Beyond the acute trauma, patients do not complain of pain. Normal erectile function has been reported after recovery from the initial event, despite persistence of nonsexual partial erection.

Etiology of Ischemic Priapism (Veno-Occlusive, Low-Flow)

Ischemic priapism accounts for the majority of cases described in the literature. The erection of ischemic priapism may begin with sexual stimulation or the administration of pharmacologic agents. Once an erection persists beyond 4 hours and is not relieved by cessation of sexual stimulation or orgasm, the physiologic phenomena of ischemic priapism have begun. Erections lasting up to 4 hours are by consensus defined as “prolonged”; manufacturers of erection-facilitating pharmacotherapies (oral, injectable, and intraurethral) recommend that the patient seek emergent medical consultation for prolonged erection.

Population-based studies estimate cases per 100,000 person-years (the number of patients with a first episode of priapism divided by the accumulated amount of person-time in the study population). Cases per 100,000 person-years have been calculated in several countries; these data depend on recording of presentations to clinics and hospitals where cases are registered. Kulmala and colleagues (1995) calculated the cases per 100,000 person-years to be 0.34 to 0.52 from 1975-1990 in Finland; Eland and colleagues (2001) calculated the cases in the Netherlands to be 1.5/100,000 person-years; Earle and colleagues (2003) calculated 0.84/100,000 person-years in Australia from 1985-2000. These reported incidences were statistically significantly impacted by the introduction and proliferation of intracavernous vasoactive injections for the management of erectile dysfunction; in Finland during the last 3 years of the study the incidence of priapism doubled to 1.1 cases/100,000 person-years. These and other reports on the epidemiology and etiology of priapism are also greatly influenced by the prevalence of SCD in the populations described. The life-time probability of a man with SCD developing ischemic priapism ranges from 29% to 42% (Emond, 1980).

In 1986 Pohl and colleagues reported on 230 cases. The etiology of priapism was identified as idiopathic in the majority, and 21% of cases were associated with alcohol or drug use/abuse, 12% with perineal trauma, and 11% with SCD (Pohl, 1986). Although SCD is a predominant etiology of veno-occlusive priapism cases in the literature, there is a wide variety of reported associations from urinary retention to insect bites (Hoover, 2004). Priapism has even been reported following spider bites and envenomation from the “Brazilian banana spider,” Phoneutria nigriventer (Andrade, 2008; Villanova, 2009). The genus Phoneutria (Greek for murderess) has eight species. P. nigriventer is known to hide in dark and moist places, wander the jungle floor, and stowaway within banana shipments. P. nigriventer is blamed for most cases of envenomation in Brazil; the venom contains a neurotoxin that has calcium channel blocking properties, inhibits glutamate release, and inhibits calcium reuptake and glutamate reuptake. Bites can cause intense pain, loss of muscle control—paralysis, breathing problems—asphyxiation, and priapism (www.wikipedia.org). Two peptides isolated from the venom of P. nigriventer have been directly linked with the induction of persistent and painful erections in mammals (Tx2-5 and TX2-6). The protein has been named eretina and has been shown to have highly specific interference at the molecular level with nitric oxide pathway (NO). Penile erection has been induced in vivo with eretina by direct intraperitoneal injection with a minimum effective dosage of 0.006 mcg/kg (Andrade, 2008).

Hematologic dyscrasias are a major risk factor for ischemic priapism. Priapism has been described as a complication of SCD, thalasssemia, hemoglobin Olmsted, and thrombophilia (Burnett, 2005). Thrombotic disease states have also been cited as precipitants of ischemic priapism: asplenism, erythropoietin use, hemodialysis with heparin use, and cessation of coumadin therapy. Intracavernous heparin given as a therapy for priapism due to rebound hypercoagulable states has actually worsened the condition (Fassbinder et al, 1976; Bschieipfer, 2001). Priapism may occur in patients with excessive white blood cell counts. The incidence of priapism in adult male patients with leukemia is 1% to 5% (Chang et al, 2003). Hyperleukocystosis causes priapism in these patients; it is believed that mechanical pressure on abdominal veins secondary to splenomegaly causes congestion of cavernous outflow and sludging of leukemic cells within the corpora cavernosa. When priapism presents in the oncology setting, evaluation and management of the predisposing condition must accompany interventions directed at the penis. In hematologic malignancies, leukaphresis and cytotoxic therapy (hydroxurea, ctosine arabinoside) may reduce the numbers of circulating white blood cells (Ponniah et al, 2004; Manuel et al, 2007). Priapism secondary to metastatic infiltrating solid lesions rather than leukemoid reaction is extremely rare. In most case reports of metastatic priapism, the primary malignancy is genitourinary (prostate and bladder). Metastatic infiltration of the penis may proceed with solid replacement or focal deposits within the corpora cavernosa, glans, and corpus spongiosum. Theoretically, metastatic deposits within the corpora could obstruct venous outflow resulting in ischemic priapism. Depending on the status of the patient, metastatic lesions may be managed expectantly, with partial or total penectomy, chemotherapy, or irradiation. These cases are too rarely and poorly described to define best practice recommendations (Robey, 1984; Chan, 1998; Guvel, 2003; Celma-Domenech, 2008) (Table 25–1).

Table 25–1 Etiologies of Priapism

Etiology of Stuttering (Intermittent) Priapism

Stuttering (intermittent) priapism describes a pattern of recurrent priapism. The term has traditionally been used to describe recurrent unwanted and painful erections in men with SCD. Patients typically awaken with an erection that persists up to 4 hours and becomes progressively painful secondary to ischemia. SCD patients may experience stuttering priapism from childhood. Any patient who has experienced ischemic priapism is at risk for stuttering priapism. Patients with stuttering priapism will experience repeated painful intermittent attacks up to several hours before remission. Affected young men suffer embarrassment, sleep deprivation, and performance anxiety with sexual partners (Chow, 2008). In a study of 130 patients with SCD, Adeyoju and colleagues (2002) reported that 46 (35%) had a history of priapism and, of these, 33 (72%) had a history of stuttering priapism. In 75% of patients the first episode of stuttering occurred before the age of 20. Two thirds of males presenting with SCD ischemic priapism will describe prior stuttering attacks (De Jesus, 2009). Commonly reported precipitants of full-blown SCD priapism are stuttering nocturnal/early morning erections, dehydration, fever, and exposure to cold.

Etiology and Pathophysiology of Nonischemic (Arterial, High-Flow) Priapism

HFP is a persistent erection caused by unregulated cavernous arterial inflow. The epidemiologic data on nonischemic priapism is almost exclusively derived from small case series or individual case reports. Nonischemic priapism is much rarer than ischemic priapism, and the etiology is largely attributed to trauma. Forces may be blunt or penetrating, resulting in laceration of the cavernous artery or one of its branches within the corpora. The etiology most commonly reported is a straddle injury to the crura. Other mechanisms include coital trauma, kicks to the penis or perineum, pelvic fractures, birth canal trauma to the newborn male, needle lacerations, complications of penile diagnostics, and vascular erosions complicating metastatic infiltration of the corpora (Witt, 1990; Brock, 1993; Dubocq, 1998; Burgu, 2007; De Jesus, 2009). Although accidential blunt trauma is the most common etiology, HFP has been described following iatrogenic injury: cold-knife urethrotomy, Nesbitt corporoplasty, and deep dorsal vein arterialization (Wolf, 1992; Liguori, 2005). Any mechanism that lacerates a cavernous artery or arteriole can produce unregulated pooling of blood in sinusoidal space with consequent erection. Nonischemic priapism is typically delayed in onset compared with the episode of blunt trauma (Ricciardi, 1993). Sustained partial erection may develop 24 hours following perineal or penile blunt trauma. It is believed that the hemodynamics of a nocturnal erection disrupts the clot and the damaged artery/arteriole ruptures; the unregulated arterial inflow creates a sinsusoidal fistula. As healing progresses with clearing of clot and necrotic smooth muscle tissue, the fistula forms a pseudocapsule. Formation of a pseudocapsule at the site of fistula may take several weeks to months.

Contemporary reports suggest that HFP may have a unique subvariety. Several authors have noted that following either aggressive medical management of ischemic priapism or surgical shunting, priapism may rapidly recur with conversion from ischemia to high flow. HFP has been reported after aspiration and injection of α-adrenergics in the management of ischemic priapism (McMahon, 2002; Rodriguez, 2006; Bertolotto, 2009). Color Doppler ultrasound has shown formation of an arteriolar-sinusoidal fistula at the site of intervention (needle laceration or shunt site) (Fig. 25–2A to C). On rare occasion following reversal of ischemic priapism, a new high-flow hemodynamic state of the cavernous arteries occurs with no evidence of fistula. This presentation of HFP should be suspected in cases where rapid recurrence, persistence of erection with partial penile rigidity, or stuttering priapism not associated with pain is evident. Nonfistula type of arterial priapism is the result of dysregulation of cavernous inflows. Nonfistula arterial priapism is a rare complication following management ischemic priapism (Seftel, 1998; Cruz-Guerra, 2004; Wallace, 2009). Penile tenderness to palpation is easily confused with the ongoing ache of persistent ischemia. Soft tissue edema and ecchymosis render the physical examination equivocal after medical and surgical maneuvers to alleviate priapism. Dysregulated arterial inflows with or without a fistula can best be distinguished from persistent ischemic priapism by color Doppler ultrasound.

Figure 25–2 A, Color duplex Doppler ultrasound, showing right cavernous arterial inflow (RCA). The patient had a 30-hour ischemic priapism reversed with a Winter shunt. He developed a persistent partial erection, converting from ischemia to high-flow priapism. B, Peak systolic velocity in right cavernous artery is 45 cm/sec. C, Arterial sinusoidal fistula has formed at the site of the previous Winter shunt, as shown in this transverse color Doppler image of the glans penis.

Priapism in Children

Priapism in children and adolescents is most commonly related to SCD. The literature suggests that the incidence of priapism in pediatric sickle cell clinics is 2% to 6% (Tarry and Duckett, 1987; De Jesus, 2009). The majority of SCD priapism is ischemic. In the newborn period, fetal hemoglobin predominates, not hemoglobin S (Burgu, 2007). SCD phenotypes related to ischemic or occlusive crises are unlikely to be evident while fetal hemoglobin persists. Newborn priapism is an extremely rare phenomenon with only limited case reports and rare application of contemporary diagnostic modalities. Erection is frequently elicited in males during the newborn period. In newborn males simple tactile stimulation such as diaper changing, bathing, and urethral catheterization may result in erection; the erection quickly subsides following cessation of stimuli. Fewer than 20 cases of newborn priapism have been reported in the literature; rarely has etiology been defined: polycythemia, blood transfusion, and birth canal trauma (Amlie, 1977; Leal, 1978; Shapiro, 1979; Walker, 1997). The majority of cases have been conservatively managed with spontaneous resolution reported from hours to days. Minimally invasive diagnostics (color Doppler ultrasound) should be performed (Pietras, 1979; Meijer, 2003). In children who develop priapism following straddle trauma, every effort should be made to localize the arteriolar-sinusoidal fistula. Hatzichristou and colleagues (2002) reported that identification of the fistula by Doppler ultrasound coupled with direct manual compression softens the high-flow erection and may speed spontaneous resolution. They suggested that this noninvasive therapy likely works in children and not adults because the perineum has considerably less subcutaneous fat and crural bodies are more easily compressed (Hatzichristou, 2002).

History

In order to initiate appropriate management, the physician must determine whether the underlying priapism hemodynamics are ischemic or nonischemic. Emergency management of ischemic priapism is recommended. Ischemia should be suspected when the patient has progressive penile pain, associated with the duration of erection; has used a known drug associated with priapism; has SCD or another blood dyscrasia; or has a known neurologic condition, especially those affecting the spinal cord. Stuttering priapism history is one of recurrent episodes of prolonged erections, usually nonresolving morning erections. Nonischemic priapism should be suspected when there is no pain and the erection duration has not been accompanied by progressive discomfort. There is a history of straddle injury, coital trauma, blunt trauma to the penis or perineum, penile injection, penile surgery or a diagnostic procedure of the pelvic and penile vessels. The onset of post-traumatic HFP in adults and children may be delayed by hours to several days following the initial injury (Table 25–2).

Table 25–2 Elements in Taking the History of Priapism

Physical Examination

Inspection and palpation of the penis is recommended to determine the extent and degree of tumescence and rigidity; the involvement of the cavernous bodies; the presence of pain; and the evidence of trauma to the perineum. In ischemic priapism the corporal bodies will be completely rigid; the glans penis and corpus spongiosum are not. Although malignancies rarely cause priapism, examination of the abdomen, testicles, perineum, rectum, and prostate may help identify a cancer primary. Malignant infiltration of the penis causes indurated nodules within or replacing corporal tissue. The subtle differences in the penile examination may be apparent to the experienced urologist but can be overlooked by emergency personnel on initial evaluation (Fig. 25–3A and B). If physical examination reveals the penis is nontender, tumesced, or partially erect, nonischemic priapism is suspected. In nonischemic priapism the corpora will be tumescent but not completely rigid. In children and adults with high-flow priapism, depending on the location of trauma and time since the traumatic event, there may be residual bruising at the perineum from straddle injury (Table 25–3).

Figure 25–3 A, Saggital MRI of the penis showing metastatic deposits of prostate cancer to the corpus cavernosum. B, Coronal MRI of the same patient. Note the proximal and distal metastic deposits of prostate cancer. C, T2-weighted MRI showing chondrosarcoma replacing corpus cavernosum.

(Courtesy of David Ralph.)

Table 25–3 Key Findings in Priapism

Laboratory Testing

Evaluation should include a CBC, WBC with blood cell differential, platelet count, and coagulation profile to assess anemia, rule out infection, detect hematologic abnormalities, and ensure that the patient can safely tolerate surgical interventions should initial medical management fail. In African-Americans a sickle cell prep and hemoglobin electrophoresis should be requested. Other hematologic abnormalities may cause priapism and should be sought if etiology is not evident: leukemia, platelet abnormalities, and thalassemia. An elevated reticulocyte count is nonspecific and may be elevated in both priapism due to SCD and thalassemia. Urine and serum toxicology panels should be done if recreational narcotic or prescription psychoactive drugs are suspected from the history. A corporal blood gas by aspiration is recommended in the emergency evaluation of priapism. The corporal blood aspirate differentiates ischemic from nonischemic priapism. Aspiration may be both diagnostic and therapeutic. Visual inspection of the color and consistency of an initial penile aspirate will reveal dark deoxygenated blood, with a “crankcase oil” appearance in ischemic priapism. The initial corporal apirate may be sent for blood gas testing to document pH, PO₂, and PCO₂ (Table 25–4). Color duplex Doppler ultrasonography should be initiated if the history suggests penile/perineal trauma or if the corporal aspirate reveals well-oxygenated blood (Fig. 25–4A and B).

Table 25–4 Typical Blood Gas Values

Figure 25–4 A, Initial corporal aspirate in ischemic priapism show dark, deoxygenated blood. Subsequent aspirations will show brighter blood as corpus cavernosum is reoxygenated by inflow. Empty syringes are from successive injections of phenylephrine. B, A butterfly needle for aspiration and injection should be placed at the penoscrotal junction. Initial failed efforts in the emergency room were due to distal placement of butterfly needle and failure to repeat aspirations.

Penile Imaging

Color duplex Doppler ultrasonography (CDU) of the penis and perineum is recommended in the evaluation of priapism. CDU is an adjunct to the corporal aspirate in differentiating ischemic from nonischemic priapism. Patients with prolonged ischemic priapism will have no blood flow in the cavernous arteries; the return of the cavernous artery waveform will accompany successful detumescence. Patients with nonischemic priapism have normal to high blood flow velocities detectable in the cavernous arteries; an effort should be made to localize the characteristic blush of color emanating from the disrupted cavernous artery/arteriole (Broderick, 2002). Examination of the entire penile shaft and perineum is recommended; this can be done with the patient supine but frog legged (Fig. 25–5). Penile arteriography should be reserved for the management of high-flow priapism, when embolization is planned; arteriography is too invasive as a diagnostic procedure to differentiate ischemic from nonischemic priapism (Burnett, 2004). The data from penile blood gas assessments become confusing following interventions. Color Doppler ultrasound should always be considered in the evaluation of a full or partial erection after treatments for ischemic priapism. The differential diagnosis includes resolved ischemia with penile edema, persistent ischemia, and conversion to high-flow state. Chiou and colleagues (2009) have recommended that to accurately categorize presentations as nonischemic or ischemic, careful interpretation of color Doppler ultrasound hemodynamics must be done in conjunction with the clinical assessment. They describe eight patients with priapism following intracavernous injection (duration ≤7 hours), all of whom showed presence of cavernous arterial inflows with varied peak systolic velocities and end-diastolic velocities. They concluded that most patients with priapism following ICI (and duration <7 hours) have a hemodynamic picture of mixed arteriogenic and veno-occlusive priapism. In their series, men with idiopathic ischemic priapism longer than 20 hours showed no detectible cavernous arterial inflows.

Figure 25–5 A, Examination of the crural bodies is required when searching for arterial sinusoidal fistula following straddle injury. B, Color Doppler image of arterial sinusoidal fistula of left cavernous artery.

There have recently been reports on the use of magnetic resonance imaging in priapism. Kirkam and colleagues (2008) noted that there are three possible roles for magnetic resonance imaging (MRI) to help in the assessment of priapism; the primary role would be in the imaging of a well-established arteriolar-sinusoidal fistula (Kirkham, 2008). The authors acknowledge a limitation of MRI is resolution; MRI cannot demonstrate small vessels as clearly as high-frequency Doppler sonography or angiography. The second would be in ischemic priapism to demonstrate the presence and extent of tissue thrombus and corporal smooth muscle infarction. Ralph (2009) used MRI in the prospective management of 50 patients with refractory ischemic priapism failing medical/surgical management from 24 to 72 hours. Patients underwent MRI to characterize the extent of smooth muscle necrosis before placement of penile prosthesis (Fig. 25–6A and B). The third role for MRI would be in the imaging of corporal metastasis mimicking priapism, or causing true ischemic priapism by obstruction of venous outflow.

Figure 25–6 A, T2-weighted MRI showing cavernous body thrombosis. B, Same patient. There is no enhancement following gadolinium infusion. At operation, extensive smooth muscle necrosis and thrombus was found. Patient had untreated ischemic priapism lasting several days.

(Courtesy of David Ralph.)

Ischemic Priapism

Historically, first aid was applied by the patient or recommended by a health practitioner unfamiliar with the hemodynamics of priapism; these interventions included ejaculation, ice packs, cold baths, and cold water enemas. Each of these remedies was thought to end erection by inducing vasoconstriction. Some historical reports advised voiding and exercise. Oral sympathomimetic drugs (etilefrine, pseudoephedrine, phenylpropanolamine, and terbutaline) have been reported to effectively reverse prolonged erection (<4 hours) initiated by intracavernous injection therapies with efficacies of 28% to 36% (Lowe, 1993). Lowe and Jarow (1993) compared oral terbutaline with pseudoephedrine or placebo in 75 patients with prolonged erection induced by intracavernous injection of Alprostadil; they reported detumescence in 38% of cases following terbutaline, 28% following pseudoephedrine, and 12% following placebo. In a follow-up study Priyadarshi (2004) specifically investigated the efficacy of oral terbutaline in the management of prolonged erection following intracavernous injections (papaverine/chlorproamazine); he administered oral terbutaline 5 mg or placebo to men with persisting erection for more than 2.5 hours. Detumescence was acheieved in 42% and 15% of cases, respectively, treated with terbutaline/placebo. Terbutaline treatment was unsuccessful in 58% of cases; all of those patients responded to intracavernous injection of an α-adrenergic. In this author’s experience, when diagnostic injections result in prolonged erections with duration from 2 to less than 4 hours, aspiration may not be necessary. An ultrafine needle and 1-mL syringe (phenylephrine 200 µg) may be used for single injection of α-adrenergic.

Oral agents are not recommended in the management of acute ischemic priapism (>4 hours). The recommended initial treatment of ischemic priapism is the decompression of the corpora cavernosa by aspiration. Aspiration will immediately soften the erection and relieve pain. Aspiration alone may relieve priapism in 36% of cases. The AUA Guidelines Panel (2003) advised that there were not sufficient data to conclude that aspiration followed by saline intracorporal irrigation was any more effective than aspiration alone (Montague, 2003). Subsequently, Ateyah (2005) reported that a combination of corporal blood aspiration and cold saline irrigation effectively terminated priapism in 66% of cases compared with aspiration alone (24%). Data to support the efficacy of cold saline are limited. Aspiration should be repeated until no more dark blood can be seen coming out from the corpora and fresh bright red blood is obtained. This process leads to a marked decrease in the intracavernous pressure, relieves pain, and resuscitates the corporal environment removing anoxic, acidotic, and hypercarbic blood. A single, large-bore, 19-gauge needle should be inserted at the peno-scrotal junction at 3 or 9 o’clock, to avoid piercing the dorsal neurovascular bundle. The surgeon should compress the penile shaft between the thumb and first digit, just below the 19-gauge needle, aspirating the shaft until it is soft. Leaving the needle in place, the shaft is permitted to refill. Compression is reapplied and aspiration repeated. These maneuvers may need to be serially repeated. Several small, empty syringes should be available (3-mL to 12-mL syringes).

Corporal aspiration, if unsuccessful, should be followed by α-adrenergic injection or irrigation. Aspiration followed by the intracavernous injection of sympathomimetic drugs is recommended by the AUA Guidelines Panel, 2003 (Montague, 2003). Sympathomimetic drugs (phenylephrine, etilephrine, ephedrine, epinephrine, norepinephrine, metaraminol) cause cavernous smooth muscle (CSM) contraction. In the laboratory, normal CSM preparations from humans, rabbits, and rodents show concentration-dependent contractions on exposure to phenylephrine, if the corporal environment is well oxygenated and has a normal pH (Broderick, 1994; Muneer, 2008). Broderick and Harkaway (1994) described time-dependent changes in the corporal environment beginning within 6 hours of persistent erection (Broderick, 1994) in humans. Animal models of ischemic priapism have demonstrated impairment in smooth muscle contraction with progressive acidosis, hypoxia, and glucopenia (Broderick, 1994; Saenz de Tejada, 1997; Munnarriz, 2006; Muneer, 2008). Corpus cavernosum specimens from patients presenting with prolonged priapism show no contractions to high-dose phenylephrine in vitro.

Phenylephrine is a selective α₁-adrenergic receptor agonist without β-mediated ionotropic and chronotropic cardiac effects; it is the agent of choice by AUA consensus recommendation (Montague, 2003; Pryor, 2004). There are no comparative trials of sympathomimetics in the management of priapism, nor are there dosage-tolerating studies to report. Case reports vary in efficacy from 43% to 81%, with time-dependent efficacies for each agent reported. Phenylephrine is usually diluted in normal saline with a concentration of 100 to 500 µg/mL and given in 1-mL dosages every 3 to 5 minutes. Dosing should be intermittent over the course of an hour. In this author’s experience phenylephrine can be concentrated as 200 µg/mL in saline and administered intermittently as 0.5 mL to 1.0 mL, every 5 to 10 minutes to a maximum dosage of 1 mg. This will permit up to 10 separate injections of 0.5 mL (100 µg each) or 5 separate injections of 1 mL (200 µg each). Aspirate the penis between successive injections by tightly pinching the shaft at the peno-scrotal junction, just below the site of needle insertion. Aspirate until distal shaft is empty. Then inject phenylephrine, releasing the compression at the peno-scrotal junction, allowing the shaft to refill with fresh blood. Extremes of age and preexisting cardiovascular diseases should be taken into consideration before intracavernous sympathomimetic dosing. Serial monitoring of blood pressure and pulse should be performed during and immediately following intracavernous injection of sympathomimetic drugs. Potential side effects of intracavernous sympathomimetics include headache, dizziness, hypertension, reflex bradycardia, tachycardia, and irregular cardiac rhythms. Davila (2008) reported subarachnoid hemorrhage in a case of SCD ischemic priapism. The patient was a 24-year-old African-American male who reported sudden and severe headache immediately following phenylephrine intracorporal dosing of 500 µg/mL repeated every 3 minutes for a total 4 mL (2000 µg = 2 mg). In 2005 in its Patient Safety News: Caution on Fatal Dosing Errors with Epinephrine (#35), the FDA reported a case of a 16-year-old boy who received 4 mL of undiluted 1:1000 epinephrine solution intracavernously to treat priapism. A 1:1,000,000 solution should have been used, so the boy received a massive overdosage; he arrested and could not be resuscitated (www.fda.gov/psn). Whichever intracavernous sympathomimetic agent is chosen for the management of ischemic priapism, urologists are well advised to consult their pharmacies and develop clear mixing and dosing protocols for safe administration (Fig. 25–7).

Figure 25–7 Algorithm for managing ischemic priapism.

SCD and hematologic malignancies are rare but important causes of ischemic priapism. Classically, treatment of SCD-induced ischemic priapism involved analgesics, hydration, oxygen, bicarbonate, and blood transfusion. However, systemic therapy alone is not effective management of SCD priapism (Rogers, 2005). A recent report suggested that blood transfusion may have no effective role in the treatment of sickle cell-induced priapism (Merritt, 2006). Reports from hematology centers suggest high success rates using penile aspiration/injection/irrigation of intracavernous sympathomimetics for SCD priapism (Mantadakis, 2000). Mantadakis and colleagues (2000) conducted a prospective trial for the management of children with SCD presenting with prolonged erection, ages 3 to 18 years (no placebo group). For erections lasting longer than 4 hours and less than 12 hours, emergency department interventions were local anesthetic, cavernous aspiration, and irrigation with 10 mL of a 1:1,000,000 solution of epinephrine. If detumescence lasted for 30 minutes, patients were discharged to home. They described 15 patients receiving 39 interventions, of which 37 were successful; 67% required only one aspiration and irrigation treatment. In the management of SCD pediatric patients with stuttering priapism, several levels of escalating intervention are necessary with parental and emergency department staff education comprising the first level. Gbadoe and colleagues (2001) described the treatment of 11 SCD patients (ages 30 months to 15 years) who presented with acute ischemic priapism or stuttering priapism. In their series of cases if the patient presented with priapism lasting less than 6 hours, aspiration and injection of 5 mg of etilefrine was given in the emergency department; for stuttering priapism, patients were given oral etilefrine 0.5 mg/kg nightly for 1 month, or 0.25 mg/kg twice daily. Patients (parents) also administered injections at home to reverse painful erection lasting longer than 1 hour. The authors reported no significant hypertension and only one case of “agitation” attributed to daily dosing.

Stuttering Priapism

Various factors need to be considered when treating stuttering priapism. Although an episode may last less than 4 hours, increasing frequency or duration of stuttering episodes may herald a major ischemic priapism. Multiple frequent visits to the emergency department to resolve the priapism are disruptive to the patient’s life and embarrassing. If attacks follow sexual activity, patients may become sexually avoidant (Adeyoju, 2002; Chow, 2008). Safety and efficacy of various treatments are poorly characterized in the literature. The side effects of recommended medications should be understood by the patient. Patients on chronic medical therapy to decrease the frequency of stuttering episodes may significantly benefit from performing a single sympathomimetic intracorporal injection at home as part of a personal treatment algorithm (Virag, 1996; Teloken, 2005). Multiple treatment options have been described: oral and injectable α-adrenergic agonists, terbutaline, digoxin, antisickling agent hydroxacabamide, estrogens, GnRH analogues, antiandrogens, baclofen, gabapentin, and recently phophodiesterase type 5 inhibitors (Chow, 2008).

Etilefrine is an α agonist available as an oral or injectable treatment in some European countries. Maximum oral dosing is 100 mg in 24 hours (Okpala, 2002). Okpala (2002) followed 18 adults (17 SCD patients and one with sickle trait), all with history of stuttering priapism. Patients were given oral etilefrine in escalating dosages from 25 mg at bedtime to a maximum of 100 mg each day. Stuttering episodes were reduced in frequency and duration in 72%. A small series of six SCD children were followed with dosing twice daily with 0.25 mg/kg of etilefrine (Gbadoe, 2002). The experience of multiple investigators using oral α-adrenergic dosing in the management of SCD stuttering ischemic priapism suggests that oral α-adrenergics at limited daily dosing should be considered in the management of stuttering priapism; drug therapy is typically initiated at bedtime.

Shunting

It is generally accepted that the longer an episode of ischemic priapism lasts, the greater the likelihood of compromised erectile function will be in the future. Previous reviews have concluded that priapism lasting longer than 24 hours was associated with a 90% ED rate (Pryor, 1982). Kulmala and colleagues (1995) reported 92% erectile function preservation among patients with ischemic priapism reversed in less than 24 hours, but only 22% preservation of erectile function among men with priapism lasting longer than 7 days. Recommendations based on well-documented erectile function outcomes are few. One recent study does document erectile function outcomes by contemporary standards (International Index of Erectile Function). Bennett and Mulhall (2008) carefully documented 39 cases of SCD priapism presenting to their emergency department over 8 years; men were routinely interviewed for erectile function status within 4 weeks of priapism/interventions. Of the 39 African-American men followed, 73% acknowledged prior episodes of stuttering; 85% had previously been diagnosed with SCD; and only 5% had been counseled in SCD clinics or were aware that priapism was a complication of SCD. A standard protocol of aspiration and phenylephrine injection was performed; shunting for failure of medical management was performed in 28%. In those patients where priapism was reversed, spontaneous erections (with or without use of sildenafil) were reported in 100% of men when priapism was reversed by 12 hours; 78% when reversed by 12 to 24 hours; and 44% when reversed by 24 to 36 hours. No patient reported spontaneous erections after priapism duration of longer than 36 hours. The International Society for Sexual Medicine Standards Committee (expert opinion) stated that shunting is to be considered for ischemic priapism events lasting 72 hours or less. Consideration should be given to foregoing a shunt in priapism events lasting longer, in particular where cavernous thrombosis is evident and no blood can be aspirated from the corporal bodies (Pryor, 2004; Mulhall, 2006).

The objective of shunt surgery is reoxygenation of the cavernous smooth muscle. The shared principle of shunt procedures is to reestablish corporal inflow by relieving venous outflow obstruction; this requires creation of a fistula between the corpora cavernosa (CC) and glans penis, CC and corpus sponsigosum, or CC and dorsal/saphenous veins. Shunt procedures are subdivided on the basis of anatomic location on the penis (Lue, 2006) (Figs. 25-8 and 25-9).

Figure 25–8 Winter shunt. A distal cavernoglanular shunt procedure is depicted by the transglanular placement of a large-bore needle or angiocatheter in the distal glans and corpus cavernosum.

(© Brady Urological Institute.)

Figure 25–9 A, A No. 11 blade is used for an Ebbehoj percutaneous cavernoglanular shunt, and a No. 10 blade is used for a T shunt. B and C, Note the differences between the Ebbehoj and T shunts. In the Ebbehoj technique the No. 11 blade leaves a straight incision into the glans and corporus cavernosum. In the creation of a T shunt the No. 10 blade is rotated 90 degrees after insertion and withdrawn. In both the percutaneous techniques deoxygenated blood is milked out of the open wounds; once bright red blood is seen, the skin is closed, leaving the deeper incision as the open fistula. In either procedure the maneuver may be repeated on the opposite corpora.

(courtesy of Tom Lue.)

A distal cavernoglanular shunt should be the first choice of shunting procedures because it is technically easier to perform than proximal shunting. Percutaneous distal shunting is less invasive than open distal shunting and can be performed with local anesthetic in the emergency department. The most recently described distal shunt (Brant, 2009) creates a T-shaped shunt between the CC and glans penis. Brant (2009) describes 13 men with priapism durations longer than 24 hours (6 of 13 had failed other distal or proximal shunt procedures). All T shunts were performed following penile anesthetic block; 12 of 13 patients were successfully reversed by initial intervention. In T shunting a No. 10 blade is placed vertically through the glans 4 mm away from the meatus; the blade pierces through the glans to CC and is rotated 90 degrees away from the urethra and removed. Deoxygenated blood is milked out of the wound. The glans is then sutured with absorbable suture. The authors recommend discharge home if the penis remains flaccid for 15 minutes. If erection returns or persists, a second T shunt is recommended on the opposite side of the meatus. In those cases where ischemic priapism has been present for more than 36 hours, the authors recommend immediate bilateral T shunts with passage of 20-Fr dilators into the fistula tract and well into the CC down to the crus. This technique is more traumatic and will require anesthetic. Burnett and Perorazio (2009) have described a similar technique to resolve ischemic priapism refractory to first-line interventions. Their procedure known as the “corporal snake” is a modification of the Al-Ghorab corporoglanular shunt (Fig. 25–10). Under general anesthetic, a 2-cm transverse incision is made on the glans; the distal tips of the rigid CC are incised and grasped with 2-0 stay sutures or Kocher clamps. Deoxygenated blood is milked out of the CC, but rather than excising a wedge of tunica and underlying CC muscle, a 7/8 Hegar dilator is advanced through each of the tunica windows proximally several centimeters to release blood and thrombus. The penis is made flaccid by repeated manual compression and release; the glans skin is then approximated with 4-0 chromic sutures; urethral catheter is placed and lightly compressive dressing is applied to the genitalia.

Figure 25–10 A-C, An open corporoglanular shunt is indicated if percutaneous shunting fails to reestablish cavernous blood inflow. The Al-Ghorab shunt requires the excision of circular cone segments of the distal tunica albuginea (5 × 5 mm).

(By permission of Mayo Foundation for Medical Education and Research. All rights reserved.)

The key factors determining successful surgical reversal of ischemic priapism are evacuation of thrombus, reestablishing cavernous inflow, and patency of shunt. Theoretically, larger open shunt procedures are likely to result in higher shunt patency rates; there are no data comparing percutaneous and open distal shunts. The surgeon must be guided by familiarity with various techniques: percutaneous shunting, open distal shunting, proximal shunting, and vein shunting. Although distal shunting can be performed with penile block and sedation in the emergency department, open shunting, especially that requiring passage of dilators into the CC, will likely require general anesthesia and an operating room suite. At the completion of the shunt, patency can be verified in the operating room and subsequently recovery room in a number of ways: bright oxygenated blood should be seen emanating from the corporal bodies; intracavernous pressures should fall; the penis should detumesce and refill with sequential compression and release; and color Doppler ultrasound will show resumption of cavernous artery inflow (Lue, 2002; Nixon, 2003; Chiou, 2009) (Table 25–5). Complications of shunting include penile edema, hematoma, infection, urethral fistula, penile necrosis, and pulmonary embolism.

Table 25–5 Assessing Corpora Cavernosa Shunt Patency

The most commonly described proximal shunt is the unilateral shunt, described by Quackles in 1964 (Fig. 25–11). Proximal corpus cavernosum to spongiosum (CC-CS) shunt procedures require a transscrotal or transperineal approach (Quackles, 1964). There are no data comparing bilateral (Sacher, 1972) and unilateral CC-CS shunts (Quackles, 1964). Typically, bilateral shunts are staggered; the right side and left side are separated by a distance of at least 1 cm in an effort to minimize the risk of urethral stricture at the point of CC-CS communication (Fig. 25–12). In cases where proximal shunt fails, some have advocated saphenous vein bypass or deep dorsal vein shunt (Fig. 25–13A and B). A wedge of tunica albuginea is removed and the vein is anastamosed end to side of CC. There are no comparative trials of vein shunting for ischemic priapism. Authors have described a significant risk of sapheno-femoral vein thrombus and pulmonary embolism with vein shunting (Kandel, 1968).

Figure 25–11 The proximal open shunt technique to establish communication between the corpus spongiosum and corpus cavernosum was first described by Quackles in 1964.

(By permission of Mayo Foundation for Medical Education and Research. All rights reserved.)

Figure 25–12 Bilateral shunts are staggered. The right and left sides are separated by a distance of at least 1 cm in an effort to minimize the risk of urethral stricture at the point of corpus cavernosum to spongiosum communication (Sacher, 1972).

(By permission of Mayo Foundation for Medical Education and Research. All rights reserved.)

Figure 25–13 A, Venous bypass to control ischemic priapism was first described by Grayhack in 1964. The Grayhack shunt mobilizes the saphenous vein below the junction of the femoral vein and anastamoses the vein end to side into the corpus cavernosum. B, Deep dorsal vein (DDV) shunt with distal ligation of DDV and anastamosis of proximal DDV to corpus cavernosum. A wedge of tunica albuginea is removed.

(By permission of Mayo Foundation for Medical Education and Research. All rights reserved.)

Immediate Implantation of Penile Prosthesis

Unfortunately the natural history of untreated ischemic priapism or priapism refractory to interventions is severe fibrosis, penile length loss, and complete ED (see Fig. 25–1). Kelami (1985) described the implantaion of the Small-Carrion penile prosthesis through an infrapubic incision in the management of postpriapic erectile dysfunction. Bertram and colleagues (1985) described six postpriapic cases of penile prosthesis; five of six men had successful implantation of semirigid prostheses. Both groups described extensive corporal fibrosis and suggested that semirigid implants were preferable because inflatable implants would not overcome the corporal fibrosis sufficiently to erect the penis. Douglas and colleagues (1990) reported on penile prosthesis in five SCD postpriapic men; they described a surgical technique of tunneling and corporal excavation. Inadvertent damage to the tunica albuginea was common, as was subsequent migration of hardware; 11 additional procedures were required following the initial implants. The average time from priapism to implant in Douglas’s series was 4 years. Monga and colleagues (1996) described implants in young SCD patients (six patients, average age 26); inflatable implants were placed to both treat ED and circumvent ongoing episodes of stuttering priapism. They suggested that both potency and recurrent episodes of ischemic priapism could be managed by “early” implantation. Some have suggested performing immediate penile prosthesis in the acute management of ischemic priapism, when the patient has failed sympathomimetic intracavenous therapies and shunting (Rees et al, 2002). There are two distinct advantages to immediate implantation: corporal fibrosis is not yet established, and penile length may be preserved. The exact time point at which prosthetic insertion becomes a reasonable option for managing ischemic priapism is unclear. Should medical management of ischemic priapism be followed by distal percutaneous shunt, by open distal shunt, and subsequently by proximal shunting before penile implant? Should men with delayed presentation of ischemic priapism and evident corporal thrombus be triaged to immediate penile implant? What is clear is that any discussion pertaining to early prosthesis insertion should be documented and include a comprehensive review of the theoretic advantages and actual risks. Compared with prosthesis insertion in a typical patient with erectile dysfunction, there are significantly higher rates of complications noted in priapism cases: infection, urethral injury, device migration, device erosion, and revision surgeries. The surgeon must be familiar with the additional technical concerns posed by weaknesses in the tunica albuginea in the region of prior shunts.

The advantages of early penile implantation in the acute management of ischemic priapism are preservation of penile length and technically easier implant insertion. Delayed placement of penile prosthesis is technically challenging due to corporal fibrosis. Ralph (2009) reported on 50 patients with ischemic priapism. All patients failed conservative management with the instillation of α-adrenergic agents (200 µg phenylephrine repeated to a maximum dosage of 1500 µg). Unsuccessful shunts were performed in 13 of 50 cases (Ralph, 2009). Mean duration of priapism was 209 hours (range 24 to 72 hours). All patients had evidence of cavernous thrombus and smooth muscle necrosis on MRI and all 50 underwent insertion of penile prosthesis in the acute setting of refractory ischemic priapism. Revision rates were significantly high 24% (12 of 50 patients). The infection rate of 6% was also notably high and likely related to multiple factors including ischemic tissues and preceding penile interventions.

Key Points

Surgical Management of Ischemic Priapism with Immediate Penile Implant

• The natural history of untreated IP or priapism refractory to interventions is severe fibrosis, penile length loss, and complete erectile dysfunction.

• The advantages of early penile implantation in the acute management of IP are preservation of penile length and easier insertion.

• Document baseline erectile function, duration of priapism, history of stuttering, and prior interventions.

• Consider penile prosthesis if:

the patient has failed aspiration and sympathomimetic intracavernous injection.

the patient has failed distal and proximal shunting.

ischemia has been present for longer than 36 hours.

• Consider an MRI before surgery or corporal biopsy at the time of implant to document corporal smooth muscle necrosis.

• There are higher rates of revision surgery and complications noted in priapism cases due to infection, urethral injury, device migration, and device erosion.